Objective:
Objective 1: Determine whether bioactive food components, such as vitamins A and D or lycopene, acting via vitamin A and D-receptor-mediated pathways and nuclear factor-kappaB signaling, exhibit dose-dependent inhibitory effects on macrophage-mediated remodeling of adipose tissue toward a pro-inflammatory phenotype in response to high fat diets in a swine model. [NP 107 Component 3, Problem Statement 3B].
Objective 2: Determine whether bioactives from food, including selenium, vitamin A, and thiol compounds, alter the immune response to model infectious organisms in mice through epigenetic changes, redox sensitive signaling pathways, and tissue remodeling by controlling cellular thiol levels, redox tone, and/or mitochondrial function. Compare responses of wild-type and genetically engineered mice with altered expression of one or more selenoproteins or proteins important for vitamin A or redox function, to identify specific proteins or pathways important for the effect of the nutrients under study on immune function and tissue remodeling. [NP 107 Component 3, Problem Statement 3B]

Approach:
For Objective 1, in vitro and in vivo porcine models will be used to test the hypothesis that vitamin A or vitamin D or metabolites of dietary compounds that signal through retinoic acid receptor signaling pathways, such as lycopene, will promote an anti-inflammatory phenotype of adipose tissue macrophages and inhibit pro-inflammatory responses of adipose tissue macrophages to inflammatory ligands via inhibition of NF-kappaB signaling and epigenetic regulation of macrophage polarization.
For Objective 2, a mouse model will be used to test the hypothesis that bioactives from food, including selenium, vitamin A, and thiol compounds, alter the immune response to model infectious organisms in mice through epigenetic changes, redox-sensitive signaling pathways, and tissue remodeling by controlling cellular thiol levels, redox tone, and/or mitochondrial function. Responses of wild-type and genetically engineered mice with altered expression of one or more selenoproteins or proteins important for vitamin A or redox function, will be used to identify specific proteins or pathways important for the effect of the nutrients under study on immune function and tissue remodeling.